Peptidic antagonists of class III semaphorins/neuropilins complexes

Abstract

The present invention concern a peptidic antagonist of class III semaphorins/neuropilins complexes comprising an amino acid sequence, which is derived from the transmembrane domain of a protein selected in the group consisting of neuropilin-1, neuropilin-2, plexin-A1, plexin-A2, plexin-A3, plexin-A4, Nr-CAM, L1-CAM, integrin Beta 1 and integrin beta 2, and including at least a GxxxG motif, eventually fused to an heterologous sequence; a nucleic acid encoding for said peptidic antagonist, a pharmaceutical composition comprising such a peptidic antagonist or a nucleic acid encoding thereof and uses thereof.

The invention claimed is: 
     
       1. A method for the treatment of a subject suffering from a disease associated with class III semaphorins/neuropilins complexes signal transduction pathways, comprising administering to the subject a pharmaceutical composition comprising a peptidic antagonist of class III semaphorins/neuropilins complexes, the peptidic antagonist
 consisting of a transmembrane domain of a protein selected from the group consisting of neuropilin-1, neuropilin-2, plexin-A1 and integrin beta 1, wherein the transmembrane domain is fused to a heterologous sequence, 
 
       wherein the disease is selected from diseases associated with excessive angiogenesis and cancers. 
     
     
       2. The method of  claim 1 , wherein administration of the pharmaceutical composition releases a concentration of the peptidic antagonist of more than 10 −12  M. 
     
     
       3. The method of  claim 1 , wherein the transmembrane domain has the amino acid sequence of the transmembrane domain of human neuropilin-1 as set forth in SEQ ID NO: 1, or of human neuropilin-2 as set forth in SEQ ID NO: 2, or of human plexin A1 as set forth in SEQ ID NO: 3 or of human integrin beta 1 as set forth in SEQ ID NO: 9. 
     
     
       4. The method according to  claim 1 , wherein the heterologous sequence allows at least one of: specific cellular location of the peptidic antagonist and improved purification yield of the peptidic antagonist.